Journal of Cardiac Failure
Volume 15, Issue 3 , Pages 171-181, April 2009

Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID Trial), a First-in-Human Phase 1/2 Clinical Trial

  • Brian E. Jaski, MD, FACC

      Affiliations

    • San Diego Cardiac Center, San Diego, California
    • Corresponding Author InformationReprint requests: Dr. Brian E. Jaski, San Diego Cardiac Center, 3131 Berger Avenue, San Diego, CA92123. Phone: (858) 244-6800; Fax: (858) 244-6909.
    • ,
  • Mariell L. Jessup, MD

      Affiliations

    • Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
    • ,
  • Donna M. Mancini, MD

      Affiliations

    • New York-Presbyterian Hospital/Columbia University Hospital, New York, New York
    • ,
  • Thomas P. Cappola, MD

      Affiliations

    • Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
    • ,
  • Daniel F. Pauly, MD, PhD

      Affiliations

    • Shands Hospital at the University of Florida, Gainesville, Florida
    • ,
  • Barry Greenberg, MD

      Affiliations

    • University of California at San Diego Medical Center, San Diego, California
    • ,
  • Kenneth Borow, MD

      Affiliations

    • Wayne, Pennsylvania
    • ,
  • Howard Dittrich, MD

      Affiliations

    • University of California at San Diego, San Diego, California
    • ,
  • Krisztina M. Zsebo, PhD

      Affiliations

    • Celladon Corporation, La Jolla, California
    • ,
  • Roger J. Hajjar, MD

      Affiliations

    • Mount Sinai School of Medicine, New York, New York
    • ,
  • on Behalf of the Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) Trial Investigators.

Received 22 November 2008; received in revised form 26 January 2009; accepted 26 January 2009.

Abstract 

Background

SERCA2a deficiency is commonly seen in advanced heart failure (HF). This study is designed to investigate safety and biological effects of enzyme replacement using gene transfer in patients with advanced HF.

Methods and Results

A total of 9 patients with advanced HF (New York Heart Association [NYHA] Class III/IV, ejection fraction [EF] ≤30%, maximal oxygen uptake [VO2 max] <16 mL·kg·min, with maximal pharmacological and device therapy) received a single intracoronary infusion of AAV1/SERCA2a in the open-label portion of this ongoing study. Doses administered ranged from 1.4×1011 to 3×1012 DNase resistant particles per patient. We present 6- to 12-month follow-up data for these patients. AAV1/SERCA2a demonstrated an acceptable safety profile in this advanced HF population. Of the 9 patients treated, several demonstrated improvements from baseline to month 6 across a number of parameters important in HF, including symptomatic (NYHA and Minnesota Living with Heart Failure Questionnaire, 5 patients), functional (6-minute walk test and VO2 max, 4 patients), biomarker (NT-ProBNP, 2 patients), and LV function/remodeling (EF and end-systolic volume, 5 patients). Of note, 2 patients who failed to improve had preexisting anti-AAV1 neutralizing antibodies.

Conclusions

Quantitative evidence of biological activity across a number of parameters important for assessing HF status could be detected in several patients without preexisting neutralizing antibodies in this open-label study, although the number of patients in each cohort is too small to conduct statistical analyses. These findings support the initiation of the Phase 2 double-blind, placebo-controlled portion of this study.

Key Words: Gene therapy, heart failure, SERCA2a, cardiovascular disease

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 31.50 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

 Funding for this study was provided by Celladon Corporation, La Jolla, CA. RJH is supported in part by grants from the National Institutes of Health: R01 HL078691, HL080498, HL 78731, HL083156, and a Leducq Transatlantic Network.

 R.J. Hajjar: Celladon Corporation, ownership interest (includes stock and stock options, and rights in patents); D.M. Mancini, Celladon Corporation, consultant/advisory board; B. Greenberg, Celladon Corporation, consultant/advisory board; H. Dittrich, Celladon Corporation, ownership interest (includes stock options), consultant/advisory board; K. Borow, Celladon Corporation, significant, consultant/advisory board; K.M. Zsebo, Celladon Corporation, employment.

PII: S1071-9164(09)00035-9

doi:10.1016/j.cardfail.2009.01.013

Journal of Cardiac Failure
Volume 15, Issue 3 , Pages 171-181, April 2009

Article Tools

* Image Usage & Resolution